Didem TURGUT, Fatih DEDE, Ezgi COŞKUN YENİGÜN, Serhan Vahit PİŞKİNPAŞA, Nihal AYDEMİR

Urinay neutrophil gelatinase-associated lipocalin as a biomarker in different renal problems

Background/aim: Neutrophil gelatinase-associated lipocalin (NGAL) is used previously to estimate the etiology, severity, and clinical outcomes of acute kidney injury (AKI). However, the role of urinary NGAL (uNGAL) in the postrenal setting is not clear. In our study, we aimed to discover the cut-off value of uNGAL that can be used in the differential diagnosis of underlying AKI etiologies. Materials and methods: In this prospective cross-sectional study, we examined 82 subjects in four groups: patients that had (1) postrenal AKI; (2) AKI other than postrenal etiologies; (3) stable chronic kidney disease; and (4) healthy subjects. A renal function assessment was carried out by measuring serum creatinine (sCr) and uNGAL at the time of diagnosis [0th min (T0)]. We followed the study group for three months. Results: At the time of diagnosis, sCr (T0) was highest in the postrenal AKI and AKI groups in contrast to stable chronic kidney disease patients and healthy subjects (P < 0.001), as expected. T0 median uNGAL was highest in the postrenal group (P < 0.001). Area under curve (AUC) of uNGAL to estimate postrenal AKI presence was 0.957 (95% CI, 0.897–1.000; P < 0.001). The cut-off point of uNGAL was 42.625 ng/mL for this estimation. Conclusion: Patients with AKI must be classified according to the underlying etiologies as soon as possible. uNGAL may be useful to estimate the etiologies, and whether the problem is acute or chronic in the course. In postrenal kidney problems, to plan the urgency of the urologic procedures, it is crucial.

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1. Rose BD. Pathophysiology of Renal Disease. 2nd ed. New York, NY, USA: McGraw-Hill; 1987. p. 41.
2. Fatehi P, Hsu C. Evaluation of acute kidney injury among hospitalized adult patients (last updated 02 October 2017). Palevsky PM (section editor), Sheridan AM (deputy editor). Waltham, MA, USA: UpToDate Inc. (Wolters Kluwer); 2018.
3. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney International Supplements 2012; 2: 8-12. doi: https://doi.org/10.1038/ kisup.2012.7
4. Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A et al. NGAL Meta-analysis Investigator Group. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. American Journal of Kidney Diseases 2009; 54: 1012-1024. doi: 10.1053/j.ajkd.2009.07.020
5. Haase-Fielitz A, Bellomo R, Devarajan P, Bennett M, Story D et al. The predictive performance of plasma neutrophil gelatinase-associated lipocalin (NGAL) increases with grade of acute kidney injury. Nephrology Dialysis Transplantation 2009; 24: 3349-3354. doi: 10.1093/ndt/gfp234
6. Kümpers P, Hafer C, Lukasz A, Lichtinghagen R, Brand K et al. Serum neutrophi lgelatinase-associated lipocalin at inception of renal replacement therapy predicts survival in critically ill patients with acute kidney injury. Critical Care 2010; 14 (1): 1-9. doi: 10.1186/cc8861
7. Herget-Rosenthal S. One step forward in the early detection of acute renal failure. Lancet 2005; 365 (9466): 1205-1206. doi: 10.1016/S0140-6736(05)74787-5
8. Soto K, Papoila AL, Coelho S, Bennett M, Ma Q et al. Plasma NGAL for the diagnosis of AKI in patients admitted from the emergency department settings. Clinical Journal of American Society of Nephrology 2013; 8 (12): 2053-2063. doi: 10.2215/ CJN.12181212
9. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N et al. Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Annals of Internal Medicine 1999; 130: 461-470. doi: 10.7326/0003-4819- 130-6-199903160-00002
10. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute Dialysis Quality Initiative Work Group. Acute renal failure— definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Critical Care 2004; 8: 204-212. doi: 10.1186/ cc2872
11. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K et al. Identification of neutrophil gelatinase-associated lipocalin as a novel earl yurinary biomarker for ischemic renal injury. Journal of American Society of Nephrology 2013; 14 (10): 2534-2543. doi: 10.1097/01.asn.0000088027.54400.c6
12. Nickolas TL, O’Rourke MJ, Yang J, Sise ME, Canetta PA et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase associated lipocalin for diagnosing acute kidney injury. Annals of Internal Medicine 2008; 148: 810-819. doi: 10.7326/0003-4819-148-11- 200806030-00003
13. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. Journal of Chronical Diseases 1987; 40: 373-383. doi: 10.1016/0021-9681(87)90171- 8
14. Ding H, He Y, Li K, Yang J, Li X et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for renal tubulointerstitial injury in IgA nephropathy. Clinical Immunology 2007; 123: 227-234. doi: 10.1016/j. clim.2007.01.010
15. Brunner HI, Mueller M, Rutherford C, Passo MH, Witte D et al. Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis and Rheumatism 2006; 54: 2577- 2584. doi: 10.1002/art.22008
16. Bolignano D, Coppolino G, Campo S, Aloisi C, Nicocia G et al. Neutrophil gelatinase-associated lipocalin in patients with autosomal-dominant polycystic kidney disease. American Journal of Nephrology 2007; 27: 373-378. doi: 10.1159/000103912
17. Singer E, Elger A, Elitok S, Kettritz R, Nickolas TL et al. Urinary neutrophil gelatinase-associated lipocalin distinguishes prerenal from intrinsic renal failure and predicts outcomes. Kidney International 2011; 80: 405-414. doi: 10.1038/ki.2011.41
18. Urbschat A, Gauer S, Paulus P, Reissig M, Weipert C et al. Serum and urinary NGAL but not KIM-1 raises in human post-renal AKI. European Journal of Clinical Investigation 2014; 44 (7): 652-659. doi: 10.1111/eci.12283
19. Wasilewska A, Taranta-Janusz K, Debek W, Zoch-Zwierz W, Kuroczycka-Saniutycz E. KIM-1 and NGAL: new markers of obstructive nephropathy. Pediatric Nephrology 2011; 26: 579- 586. doi: 10.1007/s00467-011-1773-5
20. Madsen MG, Norregaard R, Palmfeldt J, Olsen LH, Frokiaer J et al. Urinary NGAL, cystatin C, beta2-microglobulin, and osteopontin significance in hydronephrotic children. Pediatric Nephrology2012; 27: 2099-2106. doi: 10.1007/s00467-012- 2217-6
21. Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H et al. Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. Kidney International 2009; 75: 285-294. doi: 10.1038/ ki.2008.499
22. Alipour A, Mohammadjafari H, Rafiei A, Amjadi O. The role of urinary biomarker levels in assessing the presence and severity of ureteropelvic junction obstruction in children: a systematic review and meta-analysis. Journal of Pediatrics Review 2016; 4 (2): 1-11. doi: 10.17795/jpr-7567
23. Papachristou F, Pavlaki A, Printza N. Urinary and serum biomarkers in ureteropelvic junction obstruction: a systematic review. Biomarkers 2014; 19: 531-540. doi: 10.3109/1354750X.2014.943292
24. D Kostic, Beozzo GPNS, Do Couto SB, Kato AHT, Lima L et al. The role of renal biomarkers to predict the need of surgery in congenital urinary tract obstruction in infants. Journal of Pediatric Urology 2019; 15: 242-249. doi: 10.1016/j. jpurol.2019.03.009